The thyroid gland is an endocrine organ that secretes the hormones triiodothyronine (T3) and thyroxine (T4), which are, in turn, under the influence of the TSH and the TRH. Though hyper- and hypothyroidism remain the common clinically manifesting condition of the thyroid, in some cases, the patient remains symptomless with either excess or decrease in thyroxine levels, along with normal TSH levels. This is termed as euthyroid hyperthyroxinemia and euthyroid hypothyroxinemia, respectively. The cause is altogether different from the thyroid and should not be inappropriately managed as hyperthyroid and hypothyroid states.

00:01
If the previous discussion was euthyroid hyperthyroxinemia,
this discussion now brings us to euthyroidhypothyroxinemia.
00:13
Euthyroid hypothyroxinemia due to, well, if
the previous discussion was increased thyroidbinding globulin, here you’re going to have
decreased binding protein.
00:25
So, you’ll have binding protein abnormalities.
00:28
Let’s talk about those drugs.
00:31
There are a bunch of drugs here that you want
to know that will cause euthyroid hypothyroxinemia.
00:39
Drugs that displace T4 from the binding site.
00:43
So if you now displace your T4 from your TBG,
what faction are you increasing here transiently?The free.
00:54
Who is communicating with the hypothalamo-pituitary-thyroid
axis?Is it the free or the bound?It’s the free.
01:02
As far as you’re concerned to get any of
your questions correct, it is the free T4that is going to dictate how much thyroid
functioning that you’re having in the body.
01:16
Is that clear?In physiology, you’ve already talked about
T4 and you have certain experts that’llsay, “Oh, no, no, no.
01:26
It’s T3 that’s going to be responsible
for feedback mechanism.”Both individuals are correct, as far as you’re
concerned as a clinician.
01:36
That T4, the free, is going to then regulate
the feedback mechanism for your hypothalamus-pituitaryand such.
01:45
So, here, if you were displacing your T4 from
your TBG, due to the drugs such as salicylates,such as furosemide in patients with CKI (stands
for chronic kidney injury) patients, or NSAIDssuch as mefenamic acid, then you’re removing
the T4 from the bound.
02:09
The free T4 that is found to be excess is
going to slide down the axis.
02:14
You’re in the state of euthyroid, but the
total is decreased.
02:19
Why?Because these drugs removed or displaced the
T4 from your TBG.
02:28
One important cause of euthyroid or one set
of causes of euthyroid hypothyroxinemia.
02:36
Let’s talk about TBG deficiency.
02:39
It could be hereditary.
02:41
In the previous discussion there was euthyroid
hyperthyroxinemia, also hereditary, but that’dbe TBG excess.
02:50
That was XR-dominant.
02:51
Here we have XR-recessive, if you can remember.
02:56
Hormonal excess.
02:57
Which hormone is going to then shut down or
slow down release of TBG from the liver?If in hyperthyroxinemia, your oestrogen in
pregnancy that I’ve walked you through ingreat detail increase TBG and in this case
we have the androgens that are going to slowdown the release of TBG in the liver.
03:19
We have not only androgens – we have glucocorticoids
and growth hormone.
03:25
Interesting enough, these would be more or
less your stress hormones.
03:30
Acromegaly – excess growth hormone.
03:33
Glucocorticoids – stress hormone.
03:35
Welcome to cortisol, quote-unquote.
03:37
Androgen is the opposite of oestrogen in terms
of its effects on your patient.
03:45
Hormonal excess causing decreased TBG.
03:49
Nephrotic syndrome – here we have loss of
protein.
03:54
And meds - these include asparaginase, dunazol
and niacin, that may result in TBG deficiency.
04:03
Drugs are something that you want to keep
in mind.
04:05
Our next section here, I’m going to give
you more drugs that are heavily tested, clinicallyused, that cause euthyroid hypothyroxinemia
that you want to be quite aware of.
04:19
Why have I not listed these in this illustration?Because the mechanisms, as we shall see, will
be a little bit different.
04:27
Now, anticonvulsants (phenytoin, carbamazepine),
heparin – extremely interesting.
04:33
We know a lot about heparin, a lot.
04:36
Heparin, in this case, let’s say that you
have a patient who has DVT, symptoms of DVT.
04:45
And you then give heparin in a hospital setting.
04:49
How is it that heparin causes euthyroid hypothyroxinemia?It’s not that it displaces the T4 from your
TBG, like we saw in the earlier discussionwith NSAIDs, with salicylates.
05:02
It’s the fact that it increases lipoprotein
lipase.
05:09
When you increase your lipoprotein lipase,
brings you back to biochemistry, you’rethen going to break up some of that lipid,
aren’t you, such as chylomicrons and soforth.
05:21
And when you do so, you’re going to release
free fatty acids.
05:25
That free fatty acids will then inhibit the
T4 bonding resulting in euthyroid hypothyroxinemia.
05:32
Fascinating!Know it well.
05:37
The illustration earlier, I walked you through
normal binding of T4 and then I walked youthrough increased TBG and how that increases
total.
05:51
So, what’s happening here?All of the ideologies that I walked you through,
in terms of drugs or maybe it’s hereditaryand so on and so forth, maybe nephrotic syndrome,
you’re going to be losing TBG.
06:04
So, there’s TBG deficiency.
06:07
If there’s TBG deficiency, then what happens
to total?It decreases.
06:13
If your total decreases, then please understand
that you’re in a state of hypothyroxinemia.
06:18
But, why are you euthyroid?Because the feedback mechanism is still intact.
06:24
Once again, you’re focusing upon now what
is this that we’re seeing.
06:30
The resin, in how much of this resin is going
to take up that T3.
06:35
You’ll notice here that with decreased bound,
you could have excess T3 bound to resin.
06:45
Hence, the big thick black line.
06:49
Now, the way that you want to interpret this
entire section is what I’m going to showyou next with a summary table and once you’ve
gone through the summary table, you shouldhave these images in your head of euthyroid
hypothyroxinemia versus euthyroid hyperthyroxinemiaand the amount of TBG that’s available to
bind to T4.
07:15
Let us now take a look.

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